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Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents

Drug Interactions

Drug Interactions between Nucleoside Reverse Transcriptase Inhibitors and Other Drugs (Including Antiretroviral Agents)

(Last updated: July 14, 2016; last reviewed: July 14, 2016)

Table 19c. Drug Interactions Between Nucleoside Reverse Transcriptase Inhibitors and Other Drugs (Including Antiretroviral Agents)
Concomitant Drug
Class/Name
NRTI Effect on NRTI and/or Concomitant Drug Concentrations Dosage Recommendations and Clinical Comments
Non-ARV Antivirals
Adefovir TDF No data Do not coadminister. Serum concentrations of TDF and/or other renally eliminated drugs may be increased.
Ganciclovir
Valganciclovir
TDF No data Serum concentrations of these drugs and/or TDF may be increased. Monitor for dose-related toxicities.
ZDV No significant effect Potential increase in hematologic toxicities
Ledipasvir/Sofosbuvir TAF No significant effect No dosage adjustment
TDF
  • Ledipasvir ↑ TDF AUC 40% to 98% when TDF given with RPV and EFV
  • Further ↑ TDF possible if TDF given with PIs
No dose adjustment necessary. Monitor for TDF toxicity.

The safety of increased TDF exposure when ledipasvir/sofosbuvir is coadministered with TDF and a PI/r, ATV/c, or DRV/c has not been established. Consider alternative HCV or ARV drugs to avoid increased TDF toxicities. If coadministration is necessary, monitor for TDF-associated adverse reactions.

Coadministration of ledipasvir/sofosbuvir with EVG/c/TDF/FTC is not recommended.
Ribavirin ddI ↑ intracellular ddI Contraindicated. Do not coadminister. Fatal hepatic failure and other ddI-related toxicities have been reported with coadministration.
ZDV Ribavirin inhibits phosphorylation of ZDV. Avoid coadministration if possible, or closely monitor HIV virologic response and possible hematologic toxicities.
INSTIs
DTG TAF TAF AUC ↔ No dosage adjustment
TDF
  • TDF AUC
  • DTG ↔
No dosage adjustment
RAL TDF RAL AUC ↑ 49% No dosage adjustment
Narcotics/Treatment for Opioid Dependence
Buprenorphine 3TC, ddI, TDF, TAF, ZDV No significant effect No dosage adjustment
Methadone ABC methadone clearance ↑ 22% No dosage adjustment
d4T d4T AUC ↓ 23% No dosage adjustment
ZDV ZDV AUC ↑ 29% to 43% Monitor for ZDV-related adverse effects.
NNRTIs
RPV ddI RPV, ddI ↔ when RPV taken 2 hours after ddI Administer RPV with food 4 hours before or 2 hours after ddI.
NRTIs
ddI d4T No significant PK interaction Do not coadminister. Additive toxicities of peripheral neuropathy, lactic acidosis, and pancreatitis seen with this combination.
TDF ddI-EC AUC and Cmax ↑ 48% to 60% Avoid coadministration.
Other
Allopurinol ddI ddI AUC ↑ 113%

In patients with renal impairment:
  • ddI AUC ↑ 312%
Contraindicated. Potential for increased ddI-associated toxicities.
Atovaquone
ZDV ZDV AUC ↑ 31%
Monitor for ZDV-related adverse effects.
Anticonvulsants
Carbamazepine,
Oxcarbazepine,
Phenobarbital,
Phenytoin
TAF ↓ TAF possible Consider alternative anticonvulsant.
Antimycobacterial
Rifabutin,
Rifampin,
Rifapentine
TAF ↓ TAF possible Coadministration is not recommended.
Herbal Products
St. John’s wort
TAF ↓ TAF possible Coadministration is not recommended.
PIs
ATV
+/-
RTV or COBI
ddI With ddI-EC plus ATV (with food):
  • ddI AUC ↓ 34%
  • ATV no change
Administer ATV with food 2 hours before or 1 hour after ddI.
TAF TAF 10 mg with ATV/r:
TAF AUC ↑ 91%
No dosage adjustment (use TAF 25mg).
TDF With ATV (unboosted):
  • ATV AUC ↓ 25% and Cmin ↓ 23% to 40% (higher Cmin with RTV than without RTV)
  • TDF AUC ↑ 24% to 37%
Avoid concomitant use without RTV or COBI.

Dose:
  • ATV 300 mg daily plus (RTV 100 mg or COBI 150 mg) daily when coadministered with TDF 300 mg daily. 
  • If using TDF and H2 receptor antagonist in ART-experienced patients, use ATV 400 mg daily plus (RTV 100 mg or COBI 150 mg) daily.
Monitor for TDF-associated toxicity. 
ZDV With ATV (unboosted):
  • ZDV Cmin ↓ 30% and AUC ↔
Clinical significance unknown.
DVR/c TAF TAF 25 mg with DRV/c:
TAF AUC ↔
No dosage adjustment
TDF Increased TDF possible Monitor for TDF-associated toxicity.
DRV/r TAF TAF 10 mg with DRV/r:
TAF AUC ↔
No dosage adjustment
TDF TDF AUC ↑ 22% and Cmin ↑ 37%
Clinical significance unknown. Monitor for TDF toxicity.
LPV/r TAF TAF 10 mg with DRV/r:
TAF AUC ↑ 47%
No dosage adjustment
TDF
  • LPV/r AUC ↓ 15%
  • TDF AUC ↑ 34%
Clinical significance unknown. Monitor for TDF toxicity.
TPV/r ABC ABC AUC ↓ 35% to 44%
Appropriate doses for this combination have not been established.
ddI
  • ddI-EC AUC ↔ and Cmin ↓ 34%
  • TPV/r ↔
Separate doses by at least 2 hours.
TAF ↓ TAF expected Coadministration is not recommended.
TDF
  • TDF AUC ↔
  • TPV/r AUC ↓ 9% to 18% and Cmin ↓ 12% to 21%
No dosage adjustment necessary.
ZDV
  • ZDV AUC ↓ 35%
  • TPV/r AUC ↓ 31% to 43% 
Appropriate doses for this combination have not been established.
Key to Symbols: ↑ = increase, ↓ = decrease, ↔ = no change

Key to Abbreviations: 3TC = lamivudine; ABC = abacavir; ART = antiretroviral therapy; ARV = antiretroviral; ATV = atazanavir; ATC/c = atazanavir/cobicistat; AUC = area under the curve; Cmax = maximum plasma concentration; Cmin = minimum plasma concentration; COBI = cobicistat; d4T = stavudine; ddI = didanosine; DRV/c = darunavir/cobicistat; DRV/r = darunavir/ritonavir; DTG = douletegravir; EC = enteric coated; EFV = efavirenz; EFV/c/TDF/FTC = efavirenz/cobicistat/tenofovir disoproxil fumarate/emtricitabine; HCV = hepatitis C virus; INSTIs = integrase strand transfer inhibitors; LPV/r = lopinavir/ritonavir; NRTI = nucleoside reverse transcriptase inhibitor; PI = protease inhibitor; PI/r = ritonavir-boosted protease inhibitor; PK = pharmacokinetic; RAL = raltegravir; RPV = rilpivirine; RTV = ritonavir; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate; TPV/r = tipranavir/ritonavir; ZDV = zidovudine

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